The aim of this application is to establish a large registry of Australian and New Zealand multigenerational pedigrees that will underpin future international research into the aetiology, pathogenesis, prevention and treatment of colorectal cancer. A specific aim is to foster the compilation of a comprehensive data set that will allow future stratification of families into diagnostic groups based upon the underlying genetic predisposition(s). Relying on estimates of risk based upon limited clinical information such as the number of affected subjects within a family is insufficient for meaningful grouping of families. These aims will be achieved through a dual ascertainment process, one population-based and the second through colorectal cancer family clinics or other clinical services. For all families a standardized approach will be followed with respect to the collection and storage at the Operation Core (University of Queensland) of biological specimens and epidemiological, genetic, clinical, histopathological and molecular data. The program will be supported by comprehensive clinical genetic and clinical services infrastructures to ensure that families are managed and followed-up in an appropriate manner. Based on existing patterns of accrual, we aim to collect: (I) 600 high-risk families through colorectal cancer clinics (55% of this grant), (ii) 800 population-based case families (30% of this grant), (iii) 400 population-based control families (10% of this grant) and (iv) approximately 100 twin pairs in which one or both has had colorectal cancer and their families (5% of this grant). Australia and New Zealand have many similarities with the USA and are excellent countries in which to establish Colorectal Cancer Registries due to their population characteristics. These characteristics include manageable yet sufficient size, ethnically diverse, highly localised, stable, and with families that are intact and large.